Yang Xiaowen, Zhan Yiting, Li Yifei, Shen Xinzhuang, Ma Yuqiu, Liu Zongjun, Liu Yipeng, Liang Chengjin, Zhang Xiaoyuan, Yan Yehao, Shen Wenzhi
Shandong Provincial Precision Medicine Laboratory for Chronic Non-communicable Diseases, Institute of Precision Medicine, Jining Medical University, Jining, China.
College of Clinical Medicine, Jining Medical University, Jining, China.
Front Pharmacol. 2025 Apr 16;16:1543559. doi: 10.3389/fphar.2025.1543559. eCollection 2025.
The global incidence and mortality rates associated with cancer are increasing annually, presenting significant challenges in oncology, particularly regarding the efficacy and toxicity of antineoplastic agents. Additionally, mitochondria are recognized for their multifaceted roles in the progression of malignant tumors. Mitochondrial-targeting drugs offer promising avenues for cancer therapy. This study focuses on the synthesis of a mitochondrial fluorescent probe, designated Mitochondrial Probe Molecule-1 (MPM-1), and evaluates its anti-tumor effects on colon cancer (CRC) and lung cancer (LUNG) both and .
Mito Tracker Green FM staining was performed to investigate the subcellular location of MPM-1. Cell cycle assay, colony formation, EdU, assay of cell apoptosis, wound healing assay, and trans-well migration assay were utilized to confirm anticancer properties of MPM-1 . Using a xenograft mouse model, the effects of MPM-1 in tumor treatment were also identified. RNA-seq and Western blot were performed to examine the underlying mechanism of MPM-1.
The findings indicate that MPM-1 selectively targets mitochondria and exerts inhibitory effects on CRC and LUNG cells. Specifically, MPM-1 significantly reduced the proliferation and migration of lung cancer cell lines A549 and H1299, as well as colon cancer cell lines SW480 and LOVO, with IC50 values of 4.900, 7.376, 8.677, and 7.720 µM, respectively, while also promoting apoptosis. RNA-seq analysis revealed that MPM-1 exerts its broad-spectrum anticancer effects through interactions with multiple signaling pathways, including mTOR, Wnt, Hippo, PI3K/Akt, and MAPK pathways. Additionally, studies demonstrated that MPM-1 effectively inhibited tumor progression.
In summary, MPM-1 demonstrates the ability to inhibit the growth of CRC and LUNG by targeting mitochondria and modulating several signaling pathways that attenuate tumor cell migration and proliferation while promoting apoptosis. This research underscores the potential of MPM-1 as a tumor suppressor and lays a robust foundation for the future development of innovative anticancer therapies that target mitochondrial functions.
全球癌症相关的发病率和死亡率逐年上升，给肿瘤学带来了重大挑战，尤其是在抗肿瘤药物的疗效和毒性方面。此外，线粒体在恶性肿瘤进展中的多方面作用已得到认可。线粒体靶向药物为癌症治疗提供了有前景的途径。本研究重点在于合成一种线粒体荧光探针，命名为线粒体探针分子 -1（MPM-1），并评估其对结肠癌（CRC）和肺癌（LUNG）的抗肿瘤作用。
进行Mito Tracker Green FM染色以研究MPM-1的亚细胞定位。利用细胞周期分析、集落形成、EdU、细胞凋亡检测、伤口愈合检测和Transwell迁移检测来确认MPM-1的抗癌特性。使用异种移植小鼠模型，还确定了MPM-1在肿瘤治疗中的作用。进行RNA测序和蛋白质免疫印迹以研究MPM-1的潜在机制。
研究结果表明，MPM-1选择性地靶向线粒体，并对CRC和LUNG细胞发挥抑制作用。具体而言，MPM-1显著降低了肺癌细胞系A549和H1299以及结肠癌细胞系SW480和LOVO的增殖和迁移，IC50值分别为4.900、7.376、8.677和7.720 μM，同时还促进细胞凋亡。RNA测序分析表明，MPM-1通过与多种信号通路相互作用发挥其广谱抗癌作用，包括mTOR、Wnt、Hippo、PI3K/Akt和MAPK通路。此外，研究表明MPM-1有效抑制肿瘤进展。
总之，MPM-1通过靶向线粒体并调节多个信号通路，抑制CRC和LUNG的生长，这些信号通路可减弱肿瘤细胞迁移和增殖，同时促进细胞凋亡。本研究强调了MPM-1作为肿瘤抑制因子的潜力，并为未来开发靶向线粒体功能的创新抗癌疗法奠定了坚实基础。
